Vault RNA emerges as a regulator of selective autophagy

Abstract

The selective autophagic receptor SQSTM1/p62 ushers cargo to phagophores, the precursors of autophagosomes, and serves as a platform for autophagy initiation. We discovered that SQSTM1 is an RNA-binding protein that interacts with vault RNAs. Vault RNAs are small non-coding RNAs found in many eukaryotes and transcribed by POLR3 (RNA polymerase III). The levels of VTRNA1–1 (vault RNA 1-1) regulate SQSTM1-mediated autophagy and ubiquitin aggregate clearance. Vault RNA interferes with oligomerization of SQSTM1, which is in turn critical for its autophagic function. Our study uncovered a novel mode of regulation of a protein’s activity by RNA, termed riboregulation.